Despite Severe Warnings And A New Registry Program, Many Question Whether An Acne Drug Is Really Worth the Enormous Risks Posed By Accutane.

For years, Accutane has been under siege from numerous medical experts, consumer watchdog groups, and even many officials within the FDA itself because of the many serious health risks linked to the drug.

One problem associated with the current FDA approval and review process that is quite troublesome, is the dramatic increase in the harm or risk that will be tolerated when weighing the potential benefits of a new prescription drug.

Traditionally, even drugs which promised significant benefits would be subjected to greater testing over longer periods of time when significant side-effects or adverse reactions were possible. If the drug was developed to treat a relatively minor condition, the possibility of dangerous side effects usually spelled the end of the drug in terms of FDA approval for marketing.

Today, however, drugs are routinely given FDA approval without sufficient long-term testing using large study groups and without adequate warnings despite evidence of significant side-effects and adverse reactions. Drugs are also permitted to remain on the market far longer than they should be once significant problems are suspected or even confirmed.

This has repeatedly resulted either in the need for upgraded warnings one or more times after a drug is already on the market or in dangerous drugs being pulled from the market only after causing numerous serious injuries or deaths.

Probably the most alarming situation today, however, is when a drug designed to treat a relatively minor condition is approved by the FDA and permitted to remain on the market despite clear evidence of significant side effects or adverse reactions.

In such cases, the risk versus benefit equation has all but vanished from the pharmaceutical companies’ consideration and the FDA’s standards. Accutane is an example of such a drug.

For all of the positive results it might have achieved, Accutane is still nothing more than an acne drug. This fact alone has caused a wide range of critics of the drug to wonder how it has been permitted to remain on the market at all.

Recent developments with respect to the drug and the manner in which Accutane is regulated and monitored requires a fresh look at the drug and its uncanny ability to survive when other drugs used to treat far more serious conditions with considerably less serious side-effects have been pulled from the market.

Accutane is manufactured by Hoffman-LaRoche Pharmaceuticals. Its active ingredient is known as isotretinoin and it is primarily used to treat nodular acne, a condition that is resistant to other treatments, including antibiotics, and is characterized by the appearance of many nodules or cysts.

These nodules are inflammatory lesions filled with pus and get lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.

Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
• birth defects when taken by pregnant women
• psychological problems including possible suicide
• neurological problems
• stomach, bone and muscle problems
• hearing and vision problems
• problems with fats and cholesterol in the blood
• ulcerative colitis
• Crohn’s disease
• inflammatory bowel disorder
• rectal bleeding
• abdominal pain
• central nervous system injuries
• bone and muscle loss
• cardiovascular injuries
• liver and kidney damage
• pancreatitis
• immune system disorder
• lupus
• thyroid disorders
• various allergic reactions
• Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.

In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.”

This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.

By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.

Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.

The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.

As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.

In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.

Since Accutane’s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.

It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.

Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.

Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.

In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.

The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain – an area known to mediate symptoms of depression.

The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.

Just this past month, the FDA announced that there would be a new National Registry for all Accutane users that will take effect in December 2005. Both male and female patients will have to enroll in the registry as well as doctors and pharmacies.

The purpose of this registry, called iPLEDGE is to eliminate the risk of birth defects by strictly monitoring female patients to make sure that they are not pregnant when beginning treatment and that they do not become pregnant during treatment.

Until now, women of childbearing age have been required to use two forms of birth control, get two negative pregnancy tests before their first Accutane prescription, and show proof of another negative pregnancy test before each refill.

The computerized registry system will now make sure that these precautionary measures take place as each woman will have to enter this information into the registry either by phone or by internet.

While the registry doesn’t officially begin until December, it opened on August 22 in order to allow doctors, patients, and pharmacies time to understand how to use it before everyone signs on at the end of the year.

In addition to taking part in the registry, all patients will also have to read, review, and sign a document informing them of the risks associated with Accutane, specifically psychiatric side effects and pregnancy-related issues.

The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauds the recent efforts of the FDA. Still, the organization has its doubts about the new registry.

For one thing, the registry will not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.

There is also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.

In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:
• Feelings of sadness or crying spells
• Loss of interest in activities once enjoyed
• Sleeping too much or having trouble sleeping
• Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
• Change in appetite or body weight
• Trouble concentrating
• Withdrawal from family or friends
• Loss of energy
• Feelings of worthlessness or inappropriate guilt
• Thoughts of self-harm or suicide

In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.

Currently, litigation involving the following injuries is either in progress or being considered in a number of states:
• Inflammatory Bowel Disease
• Premature Closure of Growth Plates
• Birth Defects
• Ulcerative Colitis
• Crohn's Disease
• Inflammatory Bowel Syndrome
• Rectal Bleeding
• Abdominal Pain
• Central Nervous System Injuries
• Bone and Muscle Loss
• Cardiovascular Injuries
• Liver and Kidney Damage
• Pancreatitis
• Immune System Disorder
• Lupus
• Hearing and Vision Damage
• Thyroid Disorders

Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.